Abstract

S-Adenosylmethionine decarboxylase (SAMDC) is a major regulatory enzyme in the polyamine biosynthesis and is considered a potentially important drug target for the chemotherapy of proliferative and parasitic diseases. To study regulatory mechanisms which are involved in the expression of SAMDC of the free-living nematode Caenorhabditis elegans, we have isolated the SAMDC gene and cDNA. Genomic Southern-blot analysis suggests that the C. elegans SAMDC is encoded by a single-copy gene which spans 3.9 kb and consists of six exons and five introns. The first two introns are located in the 5´-untranslated region (UTR). Analyses of the 5´-flanking region of the gene revealed several consensus sequences for the binding of different transcription factors such as CBP, AP2, cMyb, VPE2 and others. The C. elegans SAMDC mRNA possesses an open reading frame (ORF) which encodes a polypeptide of 368 amino acids, corresponding to a SAMDC proenzyme with a calculated molecular mass of 42141 Da. The active form of the C. elegans SAMDC is a heterotetramer, consisting of two subunits of 32 and 10 kDa derived from cleavage of the pro-enzyme. The SAMDC mRNA has an unusually long 5´-UTR of 477 nucleotides. This region has a small ORF which could encode a putative peptide of 17 residues. Moreover, the C. elegans SAMDC mRNA is trans-spliced with the 22 nucleotides spliced leader sequence at the 5´-end.